Low-income children, particularly Mexican-Americans, are especially at high risk for early childhood caries (ECC). While caries prevalence in other age groups has been declining in past decades, it is increasing among preschool-aged children. Our research team already demonstrated fluoride varnish (FV) efficacy in preventing ECC. This proposal continues our effort with our community partners to seek effective interventions. Resin-based dental sealants have been under-utilized in preschool children because of application difficulty. New materials, such as the refined fluoride-releasing, self-bonding glass ionomer (Gl) sealant, decrease the need for meticulous tooth-surface drying during application and provide an advantage for treating young children. The goal of this project is to conduct a community-based randomized clinical trial (RCT) to determine the relative efficacy of different combinations of Gl sealants on occlusal surfaces of primary molars, FV on all teeth, and parental counseling/anticipatory guidance (C) in reducing the caries incidence/increment in 3-6-year-old children. A 2x2 factorial design RCT, stratified by study site (one dental and one non-dental), will be conducted among initially 3-year-old children. Those eligible will be randomized to four groups (C, C+FV, C+GI, C+FV+GI) and followed for 3 years. The RCT will take place at two sites serving primarily Hispanic low-income populations in Southern California: the dental facility of the San Ysidro Health Center located near the U.S.-Mexican Border and the location of our current ECC prevention RCT for 0-3 year olds and a new partnership with La Maestra Health Center, in a non-dental setting near their dental clinic. Both sites are affiliated with WIC and Head Start. Other aims are (1) to identify child, family and community-level factors affecting caries incidence/increment; (2) to assess parental acceptance of interventions, retention in the study as well as compliance with multiple treatment visits in the RCT; and (3) to compare oral-healthcare settings/delivery systems and to assess differences as they relate to intervention outcomes. Information about the non-dental setting will inform future dissemination approaches. The proposed research will continue to establish the scientific evidence base for interventions to prevent ECC among underserved communities where oral health disparities still prevail.